颅咽管瘤（CP）是一种死亡率和发病率较高的颅内肿瘤。虽然脑性瘫痪在生物学上是良性的，但它会损害下丘脑，诱发肥胖、代谢综合征和认知障碍等合并症。旨在探索肠道微生物组和血清代谢组在 CP 相关下丘脑合并症中的作用。 CP 患者的特点是香农多样性、真杆菌属、梭状芽胞杆菌属和 Roseburia 属增加，同时阿里氏菌属和拟杆菌属减少。富含 CP 的类群与血脂异常和认知能力下降呈正相关，而 CP 耗尽的类群与脂肪肝呈负相关。随后的血清代谢组学发现嘌呤代谢显着上调，综合分析表明微生物群改变与次黄嘌呤升高之间存在关联。 Rax-CreERT2::BrafV600E/::PtenFlox/ 小鼠模型的表型研究和多组学分析证实了梭菌增多和嘌呤代谢失调与下丘脑合并症的潜在相关性。为了进一步巩固这一点，进行了干预实验，发现次黄嘌呤与下丘脑合并症的严重程度和梭状芽胞杆菌的丰度共同变化，并诱导嘌呤代谢失调以及靶器官（肝脏和大脑皮层）的氧化还原失衡。总体而言，该研究证明了梭菌增多和嘌呤代谢上调作为 CP 相关下丘脑合并症特征的潜力，并揭示了梭菌增多、嘌呤代谢失调和氧化还原失衡可能介导 CP 相关下丘脑的发生和进展。 -comorbidities.© 2024 作者。 《Advanced Science》由 Wiley‐VCH GmbH 出版。

Craniopharyngioma (CP) is an intracranial tumor with high mortality and morbidity. Though biologically benign, CP will damage the hypothalamus, inducing comorbidities such as obesity, metabolic syndrome, and cognitive impairments. The roles of gut microbiome and serum metabolome in CP-associated hypothalamic comorbidities are aimed to be explored. Patients with CP are characterized by increased Shannon diversity, Eubacterium, Clostridium, and Roseburia, alongside decreased Alistipes and Bacteroides. CP-enriched taxa are positively correlated with dyslipidemia and cognitive decline, while CP-depleted taxa are negatively associated with fatty liver. Subsequent serum metabolomics identified notably up-regulated purine metabolism, and integrative analysis indicated an association between altered microbiota and elevated hypoxanthine. Phenotypic study and multi-omics analysis in the Rax-CreERT2::BrafV600E/+::PtenFlox/+ mouse model validated potential involvement of increased Clostridium and dysregulated purine metabolism in hypothalamic comorbidities. To further consolidate this, intervention experiments are performed and it is found that hypoxanthine co-variated with the severity of hypothalamic comorbidities and abundance of Clostridium, and induced dysregulated purine metabolism along with redox imbalance in target organs (liver and brain cortex). Overall, the study demonstrated the potential of increased Clostridium and up-regulated purine metabolism as signatures of CP-associated hypothalamic-comorbidities, and unveiled that elevated Clostridium, dysregulated purine metabolism, and redox imbalance may mediate the development and progression of CP-associated hypothalamic-comorbidities.© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.